Publication: Anti-inflammatory Effects Of Mesenchymal Stem Cells Derived Extracellular Vesicle In Rat Model Of Chronic Obstructive Pulmonary Disease
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Date
2022-01
Authors
Ridzuan Noridzzaida
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Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by progressive airflow obstruction associated with chronic inflammation. The current treatment strategies are focusing on improving the symptoms and quality of life but do not provide cure for the underlying caused. Recently mesenchymal stem cells (MSC)-derived extracellular vesicles (EV) is actively being investigated as a potential source of new cell-free based therapy for COPD due to it’s ability to ameliorate inflammation, however no research has been conducted to study the anti-inflammatory effects of MSC-EV in COPD model.Thus, this study aimed to assess the anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC) derived EV in a rat model of COPD. Human UC-MSC-EV were isolated and characterized by using transmission electron microscope, western blot, and nanoparticle tracking analysis. Male sprague dawley rats (n=66) age 8-9 weeks were divided into 11 groups; Naïve, Cigarette Smoke (CS), Self-healing (SH), treatment groups (CS-hUC-MSC-EV, CS-hUC-MSC, CS-hUC-MSC-CM), vehicle groups (culture media alone (MD), and phosphate buffered saline (PBS)), and control (C) group (C-hUC-MSC-EV, C-hUC-MSC, and C-hUC-MSC-conditioned media (CM)). Five groups (CS, SH, CS-hUC-MSC, CS-hUC-MSC-EV, and CS-hUC-MSC-CM) were exposed to CS from 3 cigarettes for approximately 15 minutes per session, 2 times a day at 2 hours interval, 7 days a week, for 12 weeks. Meanwhile, Naïve, and control groups were left to breathe normal air. The treatments (hUC-MSC, hUC-MSC-EV, and hUC-MSC-CM) and PBS and MD were administered at week 13. Naïve and injury group were euthanized at week 13, while treatment groups, vehicle groups, and self-healing group were euthanized at week 15. Lungs from all groups were then subjected to histological analysis by using hematoxylin and eosin (H&E) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunofluorescence staining, and microarray analysis. Increased lymphocytes count, inflammation in peribronchial and perivascular area, as well as parenchyma area, increased goblet cells count, increased emphysema, and increased p65 expression were observed in CS group as compared to Naïve group.Self-healing for two weeks did not reduce the inflammation in peribronchial and perivascular area, as well as parenchyma area. Self-healing for two weeks also did not reduce goblet cells count, emphysema, and p65 expression. In treatment groups, reduction of inflammation in peribronchial and perivascular area, as well as parenchyma area, reduced goblet cells count, and emphysema, reduced p65 expression were observed as compared to CS and SH groups. Meanwhile, the treatments did not induce inflammation or increased goblet cells count, and did not induced emphysema in rat exposed to normal air. Microarray analysis showed regulation of COPD related pathways and genes in CS, hUC-MSC-EV, hUC-MSC groups. hUC-MSC-EV, and hUC-MSC significantly regulating many genes expression including NFKB1, MAPK1, MAP2K1, JUN, PRKCZ, and P65. In conclusion, hUC-MSC-EV effectively ameliorating the CS induced inflammation and could potentially serve as a new cell-free based therapy for the treatment of COPD.
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ANTI-INFLAMMATORY EFFECTS OF MESENCHYMAL STEM , EXTRACELLULAR VESICLE IN RAT MODEL OF CHRONIC , NORIDZZAIDA RIDZUAN , Universiti Sains Malaysia , AMDI